Oval cells are produced in significant numbers inthe livers of rats in response to a variety of specific csrcinogenic and noncarcinogenic stimuli. These small interstitial cells have been shown by electron microscopy to closely resemble the ductular cells which comprise in part the canals of Hering (cholangioles) of liver. In addition, there is evedence to suggest that at least some of the oval cells are capable of differentiating into hepatocytes during certain forms of extreme hepatic injury. The specific aim of this study is to isolate oval cells in pure population from the livers of inbred rats made cholangiofibrotic during the early stages of DL-ethionine, as well as azo dye carcinogenesis, or by the chronic dietary administration of the nonhepatocarcinogen, alpha-naphthyl-iso-thiocyanate. The isolated oval cells will then be established in primary and clonal cultures, and characterized in terms of the morphology, biochemical functions (i.e., lambda-glutamyl transpeptidase activity, alpha1-fetoprotein production), their replicative activity, and their responsiveness to hormones and other modifiers of cell differentiation. In this regard, specific attention will be paid towards determining their potential to exhibit hepatocytic traits in culture and folloiwng their transplantation back into the livers or other sites of suitably prepared isologous host rats. As such, the research proposed herein represents an effort to develop a novel epithelial culture system that will be potentially useful in the study of hepatic differentiation, cell modulation, aging and carcinogenesis.